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Biomedical subjects

Yoshihiro Watanabe

Publications and source records attributed to Yoshihiro Watanabe.

At least 19 recordsLinked to original sources
PubMed2006

Gaussian-type function set without prolapse for the Dirac-Fock-Roothaan equation (II): 80Hg through 103Lr.

We present prolapse-free universal Gaussian-type basis sets for 80Hg through 103Lr. The basis set is determined so that the Dirac-Fock-Roothaan total energy should decrease monotonically toward the numerical Dirac-Fock total energy. The difference between the Dirac-Fock-Roothaan total energy and the numerical Dirac-Fock total energy is less than 3 x 10(-6) hartree for 1H through 102No, and less than 5 x 10(-6) hartree for 103Lr. The exponents of the present sets are determined in an even-tempered manner, aiming to give total energy closer to the numerical Dirac-Fock value as the expansion term increases. The recommended set is expanded by (64, 64, 64, 46, 46, 46, 46) terms for (s+, p-, p+, d-, d+, f-, f+) symmetries, respectively. A practical set with (56, 48, 48, 36, 36, 36, 36) terms is also presented.

Journal Article↗
PubMed2006

Electronic structure of the GdF molecule by frozen-core four-component relativistic configuration interaction calculations.

The electronic structure of GdF is calculated based on frozen-core four-component relativistic configuration interactions. The resulting excitation energies are fairly close to experiment and correctly designate the excited states. For instance, the existence of the experimentally inferred state at 0.55 eV above the ground state is confirmed, having Omega=132 with (4f(7)5d(+) (1)6s(+) (1)); it is 0.58 eV above the ground state according to the present calculation.

Journal Article↗
PubMed2006

Characterization of preexisting humoral immunity specific for two cancer-testis antigens overexpressed at the mRNA level in non-small cell lung cancer.

In order to establish a rationale for immunotherapy for lung cancer, we have investigated immunological characteristics of tumor-associated antigens (TAAs) discovered through molecular approaches. Preexisting Abs specific to these predicted TAAs were examined using specimens of lung pleural effusions (LPEs) and sera in non-small cell lung cancer (NSCLC) patients. The novel cancer-testis (CT) antigens L514S and L552S were highly expressed in approximately half of the NSCLC tissues and established cell lines examined. When lung cancer patients in the USA and Japan were screened, 13%, 17%, and 5% were found to have Abs specific to recombinant L514S, L552S, and NY-ESO-1 proteins, respectively, whereas 48 normal donors had no Abs to these three CT antigens. The Ab titers specific to recombinant L552S and L514S proteins were similar to, and slightly lower than, Abs specific to NY-ESO-1 in stage IV NSCLC patients. To further characterize the preexisting specific Abs, the epitopes were analyzed using 20-aa length peptides entirely covering both antigens. An epitope common to the patients' L514S-specific Abs was identified as aa 85-100 and multiple epitopes, including a major epitope (aa 141-160), were identified for L552S-specific Abs. The Ab epitopes thus identified are not found in human, animal, or bacterial proteins, other than L514S, L552S, or XAGE-1. These data clearly demonstrate that both molecularly defined CT antigens L514S and L552S are immunogenic, at least in terms of humoral responses, suggesting that both CT antigens are promising candidates for immunotherapy.

Amino Acid Sequence↗
PubMed2006

Relativistic quasidegenerate perturbation theory with four-component general multiconfiguration reference functions.

Relativistic quasidegenerate perturbation theory (QDPT) using general multiconfiguration (GMC) reference functions is developed and implemented. It is the relativistic counterpart of the nonrelativistic QDPT with GMC reference and thus retains all the advantages of the nonrelativistic GMC reference QDPT, such as applicability to any configuration space and small computational cost compared to the complete configuration-space case. The method is applied to the potential-energy curves of the ground states of I(2) and Sb(2) molecules, the excitation energies of CH(3)I, and the energies of the lowest terms of C, Si, and Ge atoms, and is shown to provide a balanced description of potential-energy curves and accurate transition energies for systems containing heavy elements and to provide much better results compared to the reference function (i.e., active space configuration interaction) level.

Journal Article↗
PubMed2005

Correlation energies for He isoelectronic sequence with Z=2-116 from four-component relativistic configuration interactions.

The relativistic correlation energies (CEs) for the He isoelectronic sequence from 2He to 116Uuh were investigated using configuration-interaction (CI) calculations. We used a large universal-type Gaussian basis set, which gives accurate Dirac-Fock total energies for the ions under consideration. In contrast to nonrelativistic CEs, the relativistic CEs decrease monotonically with increasing nuclear charge, but the p-, d-, and f-partial CEs have a hump like the relativistic Hylleraas CI.

Journal Article↗
PubMed2004

Gaussian-type function set without prolapse 1H through 83Bi for the Dirac-Fock-Roothaan equation.

We have developed prolapse free Gaussian basis sets which can be used for 1H to 83Bi, imposing the condition that the Dirac-Fock-Roothaan (DFR) total energy (TE) decreases monotonically toward the numerical DF (NDF) TE as the expansion term increases. An even-tempered basis set was assumed. The resulting sets gave |TE(DFR) - TE(NDF)| < or = 1 x 10(-6) hartree for any atoms less or equal to 83Bi; TE(NDF) = -21 565.638 345, and TE(DFR) = -21,565.638 345 +/- 0.000 001 hartree for Bi when the expansion terms are in the range (58, 58, 58, 36, 36, 36, and 36) and (72, 72, 72, 36, 36, 36, and 36) for (s+, p-, p+, d-, d+, f-, and f+) symmetries, respectively. A practical set with 44, 44, 44, 36, 36, 32, and 32 for the respective symmetries is also proposed where |TE(DFR) - TE(NDF)| < or = 4 x 10(-5).

Journal Article↗
PubMed2004

Protein disulfide isomerase suppresses the transcriptional activity of NF-kappaB.

We report here that the transcriptional activity of NF-kappaB is negatively regulated by protein disulfide isomerase (PDI). Over-expression of PDI in RAW 264.7 cells strongly suppressed the LPS-induced production of inflammatory cytokines as well as NF-kappaB-dependent luciferase activity. This negative regulation of NF-kappaB was reversed by bacitracin, a PDI inhibitor. Interestingly, NF-kappaB/DNA complex formation and phosphorylation of NF-kappaB subunits was intact in PDI-expressing cells following stimulation with LPS. In addition, PDI and another redox regulator, thioredoxin (TRX), had opposite effects on NF-kappaB-dependent gene expression: activation of the NF-kappaB pathway by TRX was suppressed by expression of PDI in a dose-dependent manner. Finally, PDI expression was induced by the anti-inflammatory cytokine IL-10, and IL-10-mediated inhibition of LPS-induced IL-6 expression was reduced by bacitracin. These findings clearly demonstrate that PDI is a negative regulator of NF-kappaB, and may act downstream of IL-10 in this signaling pathway.

Animals↗
PubMed2004

Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen.

The developmental transcription factor SOX-4 has been shown to be highly and differentially overexpressed in primary small cell lung carcinomas (SCLC). To examine the potential of SOX-4 for broad use as a lung cancer vaccine, we have evaluated the expression of SOX-4 in a panel of primary adenocarcinoma, squamous, and large cell tumor samples as well as in a panel of established small cell and non-small cell lung carcinoma tumor cell lines. SOX-4 mRNA is shown to be overexpressed in a substantial fraction of each of these lung tumor types. To examine the immunological potential of SOX-4, we have evaluated the presence of SOX-4-specific CD4 and CD8 T cells in PBMC of healthy donors and the presence of SOX4-specific Abs in sera from SCLC patients. We demonstrate the presence of both CD4 and CD8 T cells that recognize naturally processed epitopes derived from SOX-4 as well as the presence of SOX-4-specific Abs in sera from SCLC patients, but not in sera from healthy donors. The lung tumor-specific overexpression and demonstration of a comprehensive Ag-specific immune response specific for SOX-4 support the use of this molecule in the development of whole gene-, peptide-, or protein-based vaccination strategies against lung cancer. Furthermore, the identification of naturally processed T cell and Ab epitopes from SOX-4 provides valuable tools for the development of peptide-based vaccination strategies against lung cancer as well as to monitor SOX-4-specific responses in vaccinated patients.

Amino Acid Sequence↗
PubMed2004

Clinical significance of early hepatocellular carcinoma.

Early hepatocellular carcinoma (HCC) is defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable by surgery. We studied 70 patients who had a single HCC smaller than 2 cm in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up. Based on our typing system, the tumors were assigned as early HCC (n=15), overt HCC (n=52), and non-HCC tumor (n=3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P=.01). After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P=.01; P=.001, respectively): the 5-year rates of overall survival were 93% and 54% and those of recurrence-free survival were 47% and 16%, respectively. The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% confidence interval, 0.15-0.65; P=.002) and death (0.26; 0.09-0.73; P=.01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure.

Adult↗
PubMed2004

[Recurrence of screwiness (Verschrobenheit, L. Binswanger) in chronic schizophrenia--psychopathological considerations of Mitwelt oriented screwiness ("Verschrobenheit")].

In this paper, we discuss "Verschrobenheit" of chronic schizophrenia to reconsider the recurrent deviant behavior of schizophrenics. According to Binswanger, "Verschrobenheit" is one of the fundamental disturbances of schizophrenia, characterized by morbidly thorough consistency, loss of intersubjectivity and transfiguration of the dasein like a "distorted screw" in the Mitwelt. From the viewpoint of interpersonal relationships, it manifests as a difficulty in establishing one-to-one relationships with other humans. We consider that Binswanger used the word "Verschrobenheit" to refer to 2 categories of "Verschrobenheit". The first is the behavioral aspects of screwiness without delusion, which is defined by two psychopathological features: 1) a static and morbid posture, such as an autistic attitude or unnatural position held for a long time; and 2) estrangement from the Mitwelt. The other category of "Verschrobenheit" is the behavioral aspects of screwiness with delusions. Of these aspects, the least consideration has been given to the latter. In order to discuss what screwiness means, we herein present preliminary consideration of the history of the concept of "Verschrobenheit". We report 2 cases of patients with schizophrenia who, after a certain time point following hospitalization, began to exhibit eccentric behaviors not previously observed. From examination of these cases of screwiness, and the comparison of these patients' screwiness and the former classical concepts, we determined that screwiness, has two pathological features: 1) delusional discourses confusing the surrounding people, and 2) Mitwelt-orientation.

Adult↗
PubMed2003

Gaussian-type function set without prolapse for the Dirac-Fock-Roothaan equation.

A Gaussian-type function (GTF) set without a prolapse (variation collapse) is generated for the Dirac-Fock-Roothaan (DFR) equation. The test atom was mercury. The number of primitive GTFs used is between 7 and 62 (abbreviated as 7-62), 6-62, 6-62, 4-36, 4-36, 3-36, and 3-36 for s(+), p(-), p(+), d(-), d(+), f(-), and f(+) symmetries. The respective exponent parameters were determined with even-tempered manner, which requires the minimum and maximum exponents for the respective symmetries. We prepared several sets of these. The total energy (TE) given by the numerical DF (NDF) is -19648.849250 hartree; one of the present sets with largest number of expansion terms gave -19648.849251 hartree. The error (deltaTE) relative to the NDR TE is quite small. We then applied this set to the inert gas atoms Ne (10), Ar (18), Kr (36), Xe (54), Rn (86), and No (102), and also to Es (99) as the representative of the open shell atoms. The absolute values of deltaTE were at most 2.8 x 10(-6) hartree, showing the potential of this set as a universal set.

Journal Article↗
PubMed2003

Expression of multiple mRNA species for choline acetyltransferase in human T-lymphocytes.

Acetylcholine (ACh) is synthesized by choline acetyltransferase (ChAT) in cholinergic neurons. However, both ACh and mRNA for ChAT are expressed in mononuclear leukocytes and various human leukemic T-cell lines. Multiple ChAT mRNA species (R-, N0-, N1-, N2-, and M-types) having an identical coding region and different 5'-noncoding regions have been discovered in human brain and spinal cord. These mRNAs are transcribed by a combination of use of different promoter regions and alternative splicing. However, which types of ChAT mRNA species are expressed in T-lymphocytes remains to be elucidated. In the present study, we used two human leukemic T-cell lines, CCRF-CEM (CEM) and MOLT-3, which express the same ChAT mRNA as that in the nervous system. Major mRNA species in CEM were N2- and M-type, and to a lesser extent N1-type, while MOLT-3 expressed only N2-type. Neither CEM nor MOLT-3 expressed R-type mRNA. We previously found a lack of mRNA expression encoding vesicular acetylcholine transporter (VAChT) in CEM and MOLT-3, which mediates ACh transport to synaptic vesicles in cholinergic neurons. These findings suggest that the mechanisms regulating ChAT mRNA expression in T-lymphocytes differ from those in cholinergic neurons.

Carrier Proteins↗
PubMed2003

Upregulation of mRNA encoding the M5 muscarinic acetylcholine receptor in human T- and B-lymphocytes during immunological responses.

Lymphocytes possess an independent, non-neuronal cholinergic system. Moreover, both T- and B-lymphocytes express multiple muscarinic acetylcholine receptors (mAChR). To obtain a better understanding of the regulatory mechanisms governing mAChR gene expression in the lymphocytic cholinergic system, we examined the effects of lymphocyte activation on expression of mAChR mRNA. Stimulation of T- and B-lymphocytes, respectively, with T-cell activator phytohemagglutinin and B-cell activator Staphylococcus aureus Cowan I upregulated M5 mAChR mRNA expression in the CEM human leukemic T-cell line and in the Daudi B-cell line, which served as models of lymphocytes. In striking contrast, M3 and M4 mAChR mRNA expression was not affected in either cell line. Nonetheless, stimulating lymphocytes with phorbol 12-myristate 13-acetate, a protein kinase C activator, plus ionomycin, a calcium ionophore, upregulated expression of both M3 and M5 mAChR mRNA. This represents the first demonstration that immunological stimulation leads to M5 mAChR gene expression in lymphocytes.

Antibody Formation↗
PubMed2002

Characterization of KLK4 expression and detection of KLK4-specific antibody in prostate cancer patient sera.

The ability to identify prostate tumor or prostate tissue specific genes that are expressed at high levels and use their protein products as targets could greatly aid in the diagnosis and treatment of prostate cancer. Using a polymerase chain reaction (PCR)-based subtraction technique, we have recovered the recently described KLK4 (prostase) gene from human prostate cDNA. In this study, KLK4 gene expression in human prostate tumors was further characterized using cDNA quantitative PCR and immunohistochemistry, demonstrating that the gene is specifically expressed at both the mRNA and protein levels in normal human prostate tissue, and in both primary and metastatic prostate tumor samples. Quantitative mRNA analysis also demonstrated low level expression including adrenal gland, salivary gland and thyroid. Finally, it was demonstrated that prostate cancer patient sera contain antibodies that bind specifically to recombinant KLK4 protein. This antibody has been used to detect KLK4-specific peptides in epitope mapping experiments. The relatively specific expression profile and elevated level of KLK4 mRNA and protein in both tumor and normal prostate tissues, in addition to detectable KLK4-specific antibody in cancer patient sera, supports additional efforts to determine if KLK4 can play a role in the diagnosis of prostate cancer, the monitoring of residual disease, or act as a target for immunotherapy.

Antibodies↗
PubMed2002

Hepatocyte growth factor (HGF) as a rapid diagnostic marker and its potential in the prevention of acute renal rejection.

Several investigators have reported that hepatocyte growth factor (HGF) may be related to the protection or reconstruction of the kidney during acute renal rejection. To address this question, we examined the relationship between HGF and acute rejection in the following two studies with rat renal transplantation models. In study 1, the relationship between serum HGF levels and acute renal rejection in iso-, allo- and allograft with cyclosporine (CsA)-treated models was examined. In study 2, the focus was whether or not the injection of recombinant HGF can prevent acute renal rejection. Our results demonstrated that HGF levels were rapidly increased during acute rejection and that recombinant HGF effectively protected the kidney from acute rejection. These results suggest that HGF may be induced as a counter-response to the renal injury and that it can be used as a reliable indicator for the diagnosis of acute rejection. We suggest that recombinant HGF suppresses the onset of the pathological changes of acute rejection.

Acute Disease↗
PubMed2002

Evolution of water chemistry in natural acidic environments in Yangmingshan, Taiwan.

In Yangmingshan National Park, located in the northern part of the Taiwan Island, there is a very rare area where fish (Channa asiatica) live in spite of acid environments. The origin of the acid in local acid ponds and rivers and the evolution of the water chemistry are discussed on the basis of sulfur stable isotope ratios and chemical equilibria. One of the sources of the acid is sulfuric acid, which is derived from the oxidation of hydrogen sulfide in volcanic gas gushing out from fumaroles around the area and from acid deposition supplied from Taipei City. It is also derived from the oxidation of pyrite: the sulfur stable isotope ratios of delta 34S of +1@1000 to +4@1000 (relative to CDT) of sulfate in acid pond waters (pH 3-4) could be related to those of hydrogen sulfide in volcanic gas, pyrite in local pond sediments and soils, and sulfate in rain water. One acid source is sulfuric and hydrochloric acids arising in springs from geothermal activity: the delta 34S values were characterised by +13@1000 to +17@1000 sulfate-S, which was provided by a disproportionation reaction of sulfur dioxide in the depths. Another acid source could be the oxidation of iron(II). Under acidic conditions, the water-rock reaction gives rise to high concentrations of aluminium and iron. While flowing down surface streams, iron(II) is oxidised to iron(III) and then hydrolysed to cause further acidification under oxic conditions. The concentrations of iron and aluminium are controlled by redox and dissolution equilibria.

Air Pollutants↗